Chloropeptin I is a representative member of a class of macrocyclic peptides that show potent anti-HIV activity. Specifically, chloropeptin I shows micromolar inhibition of both gp120 binding and of HIV-integrase. Both of these actions represent underdeveloped areas in current HIV therapy, and therefore chloropeptin I warrants further investigation for possible drug development. This proposal outlines the enantioselective synthesis of chloropeptin I to unambiguously prove its structure and configuration. The approach will focus on the construction of the two macrocycles via macrolactamization, followed by radical cyclization, and by intramolecular nucleophilic aromatic substitution. Upon the completion of an efficient and scalable synthesis, chloropeptin analogs can be prepared with minimal alteration of the synthetic route. Access to these derivative will allow investigation of the structure activity relationship of chloropeptin I, in an effort to develop more effective inhibitors.